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Biomedical subjects

A K Lie

Publications and source records attributed to A K Lie.

At least 37 records · Page 2Linked to original sources
PubMed2001

Therapy-related myelodysplastic syndrome of recipient origin after allogeneic bone marrow transplantation for acute lymphoblastic leukaemia.

Therapy-related myelodysplastic syndrome (t-MDS) is a very rare complication of allogeneic bone marrow transplantation (BMT). A woman with T acute lymphoblastic leukaemia (T-ALL) received an allogeneic BMT from a donor with the beta-thalassaemic trait. Five years after BMT, the red cell indices returned to normal after an initial conversion to microcytosis, implying autologous haematopoietic regeneration. Seven years after BMT, thrombocytopenia developed and marrow examination confirmed t-MDS, with a characteristic karyotype 46,XX,inv(3)(q21;q26), del(5)(q13),add(17)(p11). Retrospective molecular analysis of donor/recipient chimaerism showed gradual regeneration of recipient cells after BMT, culminating at the time of t-MDS. Our findings illustrate the unusual occurrence of t-MDS after allogeneic BMT. Re-emergence of recipient haematopoesis may herald the development of a haematological malignancy different from the original neoplastic clone for which the BMT was performed.

Adolescent↗
PubMed2001

Philadelphia (Ph) chromosome-positive chronic myeloid leukaemia relapsing as Ph-negative leukaemia after allogeneic bone marrow transplantation.

Two patients with Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukaemia (CML) relapsed 1.5 and 5 years after allogeneic bone marrow transplantation (BMT). Although the leukaemias were of recipient origin, t(9;22) could no longer be detected using conventional cytogenetics/fluorescence in situ hybridization or molecularly. Both patients responded to immunotherapy with donor lymphocytes/peripheral blood stem cells, although one patient ultimately relapsed again. These patients were similar to the occurrence of Ph(-) leukaemias previously described in Ph(+) CML after treatment with interferon or autologous BMT, and might be relevant in the pathogenesis and monitoring of treatment after BMT in CML.

Adult↗
PubMed2001

Risk of haematological malignancies in HLA-B27 carriers.

Human leucocyte antigen (HLA)-B27 carriers are predisposed to inflammatory and autoimmune diseases. Among 1137 patients with haematological diseases, 59 HLA-B27 carriers were identified. Compared with 18 774 volunteers, the incidence of HLA-B27 was increased in patients with acute leukaemia (relative risk RR = 1.67, P = 0.002), for both acute myeloid leukaemia (AML) (RR) = 1.67, P = 0.007) and acute lymphoblastic leukaemia (ALL) (RR = 1.68, P = 0.094). Of all the HLA-B27 carriers, four patients had ankylosing spondylitis (AS), all with lymphoid malignancies (three ALL, one Hodgkin's disease), whereas no HLA-B27 carriers with myeloid leukaemia had AS symptoms (P = 0.006). This suggests that HLA-B27 carriers may have an increased risk of acute leukaemia and those with concomitant AS may be predisposed to lymphoid malignancies.

Acute Disease↗
PubMed2001

Association of the HLA A2-B46-DR9 haplotype with autoimmune thyroid dysfunction after bone marrow transplantation in Chinese patients.

Autoimmune thyroid disease (AITD) may occur in patients after bone marrow transplantation (BMT). At a median follow-up of 4 years, among 194 allografts and 28 autografts, four patients (three allografts, one autograft) developed AITD. All carried the human leucocyte antigen (HLA) A2-B46-DR9 haplotype, strongly associated with AITD in the Chinese population. No significant thyroid disorder was detected in 190 patients without this haplotype. The frequency of AITD in BMT patients with the HLA A2-B46-DR9 haplotype was 12.5%, with a relative risk of 7.8 times that of non-carriers (P < 0.001). The risk of AITD should be recognized in recipients with high-risk HLA haplotypes, and regular screening might be warranted.

Adult↗
PubMed2001

Radiologic manifestations of granulocytic sarcoma in adult leukemia.

OBJECTIVE: This study was conducted to summarize the clinical and radiologic presentations including pertinent imaging features of granulocytic sarcoma, a rare extramedullary tumor of acute myeloid leukemia, in 11 adult patients. CONCLUSION: In patients in our study, the clinical and radiologic manifestations of granulocytic sarcoma were variable and occurred most commonly as disease progression in acute myeloid leukemia (73% of the patients). Granulocytic sarcoma lesions were multiple soft-tissue masses with variable enhancement, recurring in nearly 50% of patients at different sites and points of time during the course of the disease. Lesions in the central nervous system, subcutaneous tissues, and genitourinary system accounted for nearly 52% of all lesions. In general, granulocytic sarcoma masses were isodense to muscle on CT scans, and isointense and hyperintense (mild to moderate) on T1- and T2-weighted MR images, respectively. The presence of peripheral rim enhancement with hypodense or hypointense centers on T1-weighted images may, however, mimic an abscess.

Acute Disease↗
PubMed2001

Unmanipulated bone marrow transplantation from one-HLA locus mismatched siblings carries high transplant-related mortality in Chinese patients.

BACKGROUND AND OBJECTIVES: We compared the outcome of bone marrow transplantation (BMT) from HLA-identical siblings (MSD) and one HLA-locus mismatched siblings (PMSD) in Chinese patients with hematologic malignancies in terms of transplant-related mortality (TRM) and disease relapse to see whether PMSD can feasibly increase the availability of donors in our population. DESIGN AND METHODS: Medical records of patients who had received a BMT from sibling donors in the Queen Mary Hospital, Hong Kong, from March 1990 to February 2000 were reviewed (MSD 326, PMSD 20). Patients and their donors were matched for HLA-A, -B and DRB1 loci using standard serologic methods as well as polymerase chain reaction-sequence specific primers. All patients received standard anti-microbials and graft -versus host disease (GVHD) prophylaxis including cyclosporin A and a short course of methotrexate. RESULTS: A total of 346 BMT patients were analyzed of whom 326 and 20 patients had received transplants from matched and one locus mismatched siblings, respectively. Patients receiving BMT from PMSD had a significantly higher TRM than those receiving their BMT from MSD (p=0.0016). Six patients received BMT from HLA-DR PMSD: one died 2 months post-BMT as a result of post-transplantation-related lymphoproliferative disease. Fourteen patients received BMT from HLA-A or -B PMSD: 11 of these patients died after a median of 5.6 months (range 0.6-13.7 months) due to severe GVHD (n=5), graft failure (n=2), bleeding (n=1), leukemic relapse (n=2) and thrombotic thrombocytopenic purpura (n=1). Two out of the three survivors had primary graft failure: one of these two required infusion of back-up marrow and the other had autologous regeneration. Patients in the PMSD group were at greater risk of developing severe GVHD than their MSD-recipient counterparts (p<0.001). There was no significant difference in the probability of disease relapse between patients who received BMT from MSD or PMSD. INTERPRETATION AND CONCLUSIONS: BMT from PMSD (especially those with mismatches at HLA class I loci) carried a higher risk of TRM and morbidity than BMT from MSD in our population.

Adolescent↗
PubMed2001

Helper T-lymphocyte precursor frequency predicts the occurrence of graft-versus-host disease and disease relapse after allogeneic bone marrow transplantation from HLA-identical siblings.

BACKGROUND AND OBJECTIVES: Donor helper T-lymphocytes may be involved in graft-versus-host disease (GVHD) and a graft-versus-leukemia effect after bone marrow transplantation (BMT). We assayed donor helper T-lymphocyte precursor frequencies (HTLP(f)) to see whether they could predict the severity of GVHD and disease relapse after transplantation, thereby facilitating donor selection, pre-transplant counselling and modification of GVHD prophylaxis after BMT. DESIGN AND METHODS: Thirty-six consecutive adult BMT recipients and their HLA-identical sibling donors were recruited. HTLP((f)) was measured as a function of interleukin-2 secretion by alloreactive donor T-cells using a limiting dilution assay. Patients were followed prospectively to assess the severity of GVHD and the status of the primary disease after BMT. RESULTS: Eight donors had HTLP((f)) less than or equal to 10(-6); no recipients of these grafts developed severe GVHD after transplantation. Twenty-eight donors had HTLP(f) greater than 10(-6) and 18 recipients of these grafts developed severe GVHD (> or = grade 2) (chi(2) test, p<0.01). Seven donors had HTLP(f) greater than 10(-5) and no recipient had disease relapse. Twenty-nine donors had HTLP(f) less than or equal to 10(-5), 11 recipients of these grafts developed disease relapse (chi(2) test, p=0.08). INTERPRETATION AND CONCLUSIONS: BMT recipients from HLA-identical sibling donors with low (<10(-6)) and high (>10(-5)) HTLP(f) may have a low risk of acute GVHD and disease relapse after transplantation.

Adolescent↗
PubMed2001

Invasive disease due to Mucorales: a case report and review of the literature.

OBJECTIVE: To review the mycology, pathogenesis, clinical characteristics, investigations, and treatment modalities of mucormycosis. DATA SOURCES: A local case of mucormycosis; MEDLINE and non-MEDLINE search of the literature. STUDY SELECTION: Key words for the literature search were 'mucormycosis' and 'Mucorales'; all available years of study were reviewed. DATA EXTRACTION: Original articles, review papers, meta-analyses, and relevant book chapters were reviewed. DATA SYNTHESIS: Mucormycosis is a fungal infection that is rare but increasingly recognised in the growing population of immunocompromised patients. It is caused by saprophytic non-septate hyphae of the order Mucorales. The pulmonary and disseminated forms commonly occur in patients with haematological malignancy, especially acute leukaemia and lymphoma, and those receiving treatment with immunosuppressive effects. The rhinocerebral form is more prevalent in patients with diabetes mellitus, particularly those with the complication of diabetic ketoacidosis. The use of amphotericin B combined with surgery remains the mainstay of treatment. The prognosis largely depends on prompt correction of the underlying risk factors. New strategies to combat this life-threatening infection will result from better understanding of its pathogenesis. CONCLUSION: A high index of suspicion is needed, in appropriate clinical settings, to diagnose and aggressively treat this infection in view of the high mortality rate for susceptible patients.

Humans↗
PubMed2001

Plasma nitric oxide is associated with the occurrence of moderate to severe acute graft-versus-host disease in haemopoietic stem cell transplant recipients.

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) has been implicated as one of the mediators of acute graft-versus-host disease (GVHD) but reports on its measurement during haemopoietic stem cell transplantation (HSCT) in human are scarce. The present study was conducted to measure the plasma NO in HSCT recipients in order to delineate its relationships with acute GVHD. DESIGN AND METHODS: Thirty-nine randomly selected patients undergoing HSCT were recruited. Thirty-one patients received allogeneic transplants (ALLO) from HLA-identical siblings (n=20), haploidentical parent (n=1) and matched unrelated donors (n=10). Eight patients received autologous (AUTO) HSCT. Plasma levels of nitrite/nitrate (NO(2)(-)/NO(3)(-)), the end-product of NO, were measured by chemiluminescence and the results were correlated with the occurrence and severity of acute GVHD. RESULTS: Baseline NO(2)(-)/NO(3)(-) levels before HSCT were similar in the ALLO and AUTO patients (17.4 vs 21.1 microL, p>0.05). Significant increases in plasma NO(2)(-)/NO(3)(-) (> 2 times the baseline level) were found in all 13 patients with acute GVHD > or = grade 2, in 15 out of 18 patients with acute GVHD grade < or = 1 and 3 out of 8 patients receiving autologous HSCT. The increase in NO(2)(-)/NO(3)(-) among the three groups of patients was significantly different (135.5 vs 56.3 vs 36.6 micromol/L, p < 0.001). The average NO production, calculated as the area under the curve, was also significantly differently among the three groups of patients (44.5 vs 30.0 vs 23.8 micromol/L, p < 0.001). INTERPRETATION AND CONCLUSIONS: Plasma NO in HSCT recipients is quantitatively associated with the occurrence of acute GVHD and its role remains to be determined.

Adolescent↗
PubMed2000

[Human papillomavirus as a risk factor in carcinogenesis].

BACKGROUND: The causal link between Human papillomavirus (HPV) and cervical neoplasia has been established through clinical, epidemiological and molecular studies during the last two decades. In 1995, HPV 16 and 18 were classified as human carcinogens. MATERIALS AND METHODS: This paper discusses the aetiological role of HPV infection in carcinomas of the anogenital region, the respiratory and the upper digestive tract on the basis of a literature search and the author's own research. RESULTS: Almost all patients with cervical carcinomas and precursor lesions are HPV-positive. HPV is a necessary, but not sufficient factor in carcinogenesis. Several risk factors such as other sexually transmitted diseases, sexual activity, smoking, immunosuppression and diet may be important. High prevalences of HPV-DNA have also been found in carcinomas of other anogenital regions; however, HPV does not seem to be important in prostate carcinogenesis. Recent studies have shown that HPV may be a risk factor in carcinogenesis in the respiratory and upper digestive tract, but its aetiological role has yet to be proved. INTERPRETATION: Therapeutic and prophylactic vaccination is now being developed. In a few years time they may influence the treatment and prophylaxis of cervical carcinomas, some of the most common cancers among women worldwide.

Anus Neoplasms↗
PubMed2000

A case-controlled study on the use of HBsAg-positive donors for allogeneic hematopoietic cell transplantation.

To compare the clinical and serological outcomes of patients receiving donors' marrow positive or negative for hepatitis B surface antigen (HBsAg), we studied 18 patients of allogeneic hematopoietic cell transplantation receiving HBsAg-positive marrow (group 1) and 18 receiving HBsAg-negative marrow (group 2). The recipients of the 2 groups were matched for hepatitis B virus (HBV) serology, sex, age, underlying hematological diseases, conditioning regimen, and prophylaxis against graft-versus-host diseases. Eight (44.4%) recipients in group 1 and 2 (11.1%) in group 2 suffered from HBV-related hepatitis posttransplant (P =.03). Furthermore, HBV-related hepatic failure was seen in 6 group 1 patients, but in none of the group 2 patients (P =.007). Five of the 9 (55.5%) HBsAg-negative recipients in group 1 became positive after receiving HBsAg-positive marrow. Serum HBV DNA was positive in all 5 donors of these patients, but in none of the donors of recipients who remained HBsAg negative (P =.008). Group 1 patients developing HBV-related hepatitis posttransplant were more likely to have a donor carrying a precore A(1896 )and/or core promoter T(1762)/A(1764) HBV variant (62. 5% versus 0%, P =.007). This study has demonstrated that a high incidence of HBV-related hepatitis was associated with the use of HBsAg-positive marrow for transplant, and a high viral load in the donor appeared to predispose recipients to the development of HBV-related hepatitis posttransplant. Further clinical trials will be necessary to determine the optimal management approach to this problem, including the use of the antiviral agents in the donors and the recipients. (Blood. 2000;96:452-458)

Adolescent↗
PubMed2000

[DNA analyses in diagnostic pathology].

Since the publication of the polymerase chain reaction (PCR) technique in 1985, there has been an explosion of reports on its use in medicine and science. In this overview the use and limitations of PCR in diagnostic pathology are discussed. As biopsies get smaller, molecular technology will play an ever greater role in improving diagnostic accuracy. PCR is useful in tumour characterisation by assessment of clonality and detection of specific chromosomal rearrangements. This way better targeting of therapeutic intervention is possible. The value of PCR in the diagnosis of cancer, HLA typing and the detection of microorganisms is illustrated by some case reports.

Adult↗
PubMed2000

Effects of antioxidants and a caspase inhibitor on chloramphenicol-induced toxicity of human bone marrow and HL-60 cells.

Chloramphenicol (CAP), a board spectrum antibiotic widely used in many developing countries, has toxic side effects on bone marrow, the most serious of which is aplastic anemia. Recent studies suggest that effects of CAP on suppressing hematopoietic colony formation may be abrogated by antioxidants. In addition, there is preliminary evidence that CAP induces apoptosis in hemopoietic stem cells, leading to aplastic anemia. We have been unable to demonstrate the protective effects of a variety of antioxidants on CAP-induced suppression of burst-forming unit erythroid (BFU-E) and colony-forming unit granulocyte/monocyte (CFU-GM). Using flow cytometry, we have, however, confirmed that CAP can induce apoptosis in purified human bone marrow CD34+ cells. We also showed that a caspase inhibitor, Z-VAD.fmk, can ameliorate the apoptotic-inducing effects of CAP in the HL-60 cell line.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Tacrolimus (FK 506) induced thrombotic thrombocytopenic purpura after ABO mismatched second liver transplantation: salvage with plasmapheresis and prostacyclin.

We report the course of thrombotic thrombocytopenic purpura (TTP) in a patient receiving tacrolimus (FK506) immunosuppression for an ABO mismatched second liver graft. A Chinese woman with fulminant hepatitis-B reactivation failed a living-related orthotopic liver transplantation (OLT) due to portal vein thrombosis. An ABO mismatched cadaveric OLT (group A to O) was performed, with peri-operative plasmapheresis to reduce anti-A hemagglutinin titers. On day 30, she developed fever, hemolysis, thrombocytopenia and neurologic dulling. Prominent microangiopathic features in peripheral blood film, and characteristic brain lesions on magnetic resonance imaging confirmed TTP. She responded initially to intensive plasmapheresis with cryosupernatant replacement, and withdrawal of FK506. An attempted reintroduction of FK506 for threatened rejection led to TTP exacerbation. This was controlled with prolonged plasmapheresis and a ten-day infusion of prostacyclin. Immunosuppression was changed to mycophenolate mofetil. By day 53, the peripheral film and lactate dehydrogenase level had returned to baseline and plasmapheresis was stopped.

ABO Blood-Group System↗